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KMID : 0043320110340040635
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Archives of Pharmacal Research
2011 Volume.34 No. 4 p.635 ~ p.643
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Contribution of Epstein-Barr virus infection to chemoresistance of gastric carcinoma cells to 5-fluorouracil
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Seo Jung-Seon
Kim Tai-Gyu
Hong Young-Seon
Chen Jen Yang
Lee Suk-Kyeong
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Abstract
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Although Epstein-Barr virus (EBV) is associated with 6?16% of the gastric carcinoma (GC) cases, the effect of EBV infection on the tumorigenesis process and the responsiveness to chemotherapy remain unclear. We compared chemosensitivity of the EBV-positive GC (AGSEBV) and EBV-negative GC (AGS) cells to 5-fluorouracil (5-FU). Although 5-FU inhibited the growth of both cell lines in a dose- and time-dependent manner, the sensitivity of EBV-positive GC cells to 5-FU was lower than that of EBV-negative GC cells. The cleavage of PARP and caspase-3 was also lower in AGS-EBV cells than in AGS cells following 5-FU treatment. Both the level of Bcl-2 expression and the ratio of Bcl-2/Bax were higher in AGS-EBV than in AGS cells not only at basal state but also following 5-FU treatment. Moreover, p53 and p21 expression was enhanced further by 5-FU in AGS than in AGS-EBV cells. Immunofluorescence assay and Western blot showed that 5-FU induced the expression of EBV-lytic genes including BZLF1, BRLF1, BMRF1 and BHRF1. Our results suggest that latent and lytic EBV infection contributes to the chemoresistance to 5-FU in gastric carcinoma by modulating apoptosis related cellular genes.
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KEYWORD
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Epstein-Barr virus (EBV), Gastric carcinoma, 5-FU, Chemoresistance, Apoptosis, EBV-lytic genes
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